Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.Leukemia advance online publication, 23 December 2014; doi:10.1038/leu.2014.332.

Is the lateral extension of the acromion related to the outcome of shoulder injections?

OBJECTIVE To assess patients' outcomes after subacromial or glenohumeral injections based on the degree of lateral extension of the acromion. METHODS 307 patients were prospectively included after therapeutic fluoroscopy-guided subacromial (n = 148) or glenohumeral (n = 159) injections with anaesthetic and long-acting corticosteroids. Pre- and post-injection outcomes at 1 week and 1 month were obtained using the 11-point numerical rating scale (NRS) for pain. Lateral extension of the acromion was quantified and categorized by the critical shoulder angle (CSA) and the acromion index (AI) on anteroposterior conventional radiographs. RESULTS Patients' outcomes at 1 week and 1 month were significantly improved (p < 0.001) compared to baseline for subacromial and glenohumeral injection patients. Patients with a CSA <35° showed significantly higher pain reduction 1 month after subacromial injection compared to patients with a CSA >35° (4.2 ± 2.6 vs. 3.2 ± 3.0, p = 0.04). A significant difference in the 1-month NRS change in pain scores is noted for smaller AIs after subacromial injection (4.3 ± 2.8 vs. 2.6 ± 2.9; p = 0.01). No significant association was noted between clinical outcome and the lateral extension of the acromion after glenohumeral joint injections. CONCLUSIONS A short lateral extension of the acromion was associated with better clinical outcomes in subacromial injection patients but not in glenohumeral injection patients. KEY POINTS • Patients' outcomes at 1 month improved significantly compared to baseline for subacromial injections. • Patients' outcomes at 1 month improved significantly compared to baseline for glenohumeral injections. • Short acromial lateralization was associated with better clinical outcome after subacromial injection. • The acromial lateralization was not associated with clinical outcome after glenohumeral injection.

Response to neoadjuvant treatment of invasive ductal breast carcinomas including outcome evaluation: MRI analysis by an automatic CAD system in comparison to visual evaluation

BACKGROUND The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND METHODS Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases. RESULTS Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually). CONCLUSIONS In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant.

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.

Cortical reorganisation of cerebral networks after childhood stroke: impact on outcome.

BACKGROUND Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome.

Tumor budding (single tumor cells or small tumor cell clusters) at the invasion front of colorectal cancer (CRC) is an adverse prognostic indicator linked to epithelial-mesenchymal transition. This study characterized the immunogenicity of tumor buds by analyzing the expression of the major histocompatibility complex (MHC) class I in the invasive tumor cell compartment. We hypothesized that maintenance of a functional MHC-I antigen presentation pathway, activation of CD8+ T-cells, and release of antitumoral effector molecules such as cytotoxic granule-associated RNA binding protein (TIA1) in the tumor microenvironment can counter tumor budding and favor prolonged patient outcome. Therefore, a well-characterized multipunch tissue microarray of 220 CRCs was profiled for MHC-I, CD8, and TIA1 by immunohistochemistry. Topographic expression analysis of MHC-I was performed using whole tissue sections (n = 100). Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations, mismatch repair (MMR) protein expression, and CpG-island methylator phenotype (CIMP) were investigated. Our results demonstrated that membranous MHC-I expression is frequently down-regulated in the process of invasion. Maintained MHC-I at the invasion front strongly predicted low-grade tumor budding (P = 0.0004). Triple-positive MHC-I/CD8/TIA1 in the tumor microenvironment predicted early T-stage (P = 0.0031), absence of lymph node metastasis (P = 0.0348), lymphatic (P = 0.0119) and venous invasion (P = 0.006), and highly favorable 5-year survival (90.9% vs 39.3% in triple-negative patients; P = 0.0032). MHC-I loss was frequent in KRAS-mutated, CD8+ CRC (P = 0.0228). No relationship was observed with CIMP, MMR, or BRAF mutation. In conclusion, tumor buds may evade immune recognition through downregulation of membranous MHC-I. A combined profile of MHC-I/CD8/TIA1 improves the prognostic value of antitumoral effector cells and should be preferred to a single marker approach.

The Impact of Pre-Operative Malperfusion on Outcome in Acute Type A Aortic Dissection: Results From the GERAADA Registry

BACKGROUND Malperfusion adversely affects outcomes in patients with acute type A aortic dissection, but reliable quantitative data are lacking. OBJECTIVES The aim of this study was to analyze the impact of various forms of malperfusion on early outcome. METHODS A total of 2,137 consecutive patients enrolled in GERAADA (German Registry for Acute Aortic Dissection Type A) who underwent surgery between 2006 and 2010, of whom 717 (33.6%) had any kind of pre-operative malperfusion, were retrospectively analyzed. RESULTS All-cause 30-day mortality was 16.9% and varied substantially according to the number of organ systems affected by malperfusion (none, 12.6%; 1 system, 21.3%; 2 systems, 30.9%; 3 systems, 43.4%; p < 0.001). Pre-operative cerebral malperfusion, comatose state, peripheral malperfusion, visceral malperfusion, involvement of supra-aortic branches, coronary malperfusion, and renal malperfusion were all independent predictors of developing any post-operative malperfusion syndrome. When survival was considered, age, peripheral malperfusion, involvement of supra-aortic branches, coronary malperfusion, spinal malperfusion, a primary entry in the descending aorta, and pre-operative comatose state were independent predictors, again with increasing significance. CONCLUSIONS Malperfusion remains a severe clinical condition with strong potential for adverse outcomes in patients undergoing surgery for acute type A aortic dissection. The GERAADA registry suggests that the impact of the number of organs involved and the type of malperfusion on outcome differs substantially. Introducing an appropriate classification system, such as "complicated" and uncomplicated" acute type A aortic dissection, might help predict individual risk as well as select a surgical strategy that may quickly resolve malperfusion.

Cognitive remediation therapy: Does it generalize to significant outcome areas?

Objective: Cognitive remediation therapy (CRT) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia. However, there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome and negative symptoms. Method: This 8-site randomized controlled trial evaluated the efficacy of a novel cognitive-behavioral group therapy approach called integrated neurocognitive therapy (INT). INT includes manual-based exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative by compensation and restitution. One hundred and fifty-six outpatients with a diagnosis of schizophrenia or schizoaffective disorder accord- ing to DSM-IV-TR were randomly assigned to receive 15 weeks of INT or treatment as usual (TAU). INT patients received 30 bi-weekly therapy sessions. Each session lasted 90min. Mixed models were applied to assess changes in neurocognition, social cognition, symptoms, and functional outcome at post-treatment and at 9-month follow-up. Results: Compared to TAU, INT patients showed significant improvements on multiple neuro- and social-cognitive domains, negative symptoms, and functional outcome after therapy and at 9-month follow-up. Number-needed-to-treat analyses indicate that only five INT patients are necessary to produce durable and meaningful improvements in functional outcome. Conclusions: Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome and negative symptoms. These findings are important as treatment guidelines for schizophrenia have criticized CRT for their poor generalization effects.

Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE I.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

Abstract We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms.

Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently - unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain.

Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome.

BACKGROUND Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. METHODS We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. RESULTS Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality. CONCLUSION Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.

THE INHIBITORY EFFECTS OF VSV INFECTION ON MULV PRODUCTION OCCUR BETWEEN SYNTHESIS AND RELEASE OF MULV GENOMIC RNA

The inhibitory effects of VSV infection on MuLV production were investigated using the VSV temperature-sensitive mutants t1B17(I & V), tsT1026(I), tsG22(II), and ts052(II). At the permissive temperature, all four mutants suppressed the release of virion-associated MuLV gRNA by approximately 98% within 0.5 to 2.5 hr post infection. At the restrictive temperature and in the absence of cell killing, infection with t1B17(I & V) inhibited the release of MuLV gRNA, while tsT1026(I) and tsG22(II) did not. In contrast, ts052(II) inhibited the release of MuLV gRNA and induced cell killing. During the same time period and at either temperature, all four mutants did not suppress either MuLV-associated protein release or intracellular MuLV sRNA synthesis. These results indicate that VSV inhibits MULV gRNA release at a level somewhere between the synthesis and release of newly synthesized gRNA.^

Multiple retinal detachment surgery: A functional outcome study. The Houston Vision Assessment Test-Retina (HVAT-Retina)

Retinal detachment is a common ophthalmologic procedure, and outcome is typically measured by a single factor-improvement in visual acuity. Health related functional outcome testing, which quantifies patient's self-reported perception of impairment, can be integrated with objective clinical findings. Based on the patient's self-assessed lifestyle impairment, the physician and patient together can make an informed decision on the treatment that is most likely to benefit the patient. ^ A functional outcome test (the Houston Vision Assessment Test-Retina; HVAT-Retina) was developed and validated in patients with multiple retinal detachments in the same eye. The HVAT-Retina divides an estimated total impairment into subcomponents: contribution of visual disability (potentially correctable by retinal detachment surgery) and nonvisual physical disabilities (co-morbidities not affected by retinal detachment surgery. ^ Seventy-six patients participated in this prospective multicenter study. Seven patients were excluded from the analysis because they were not certain of their answers. Cronbach's alpha coefficient was 0.91 for presurgery HVAT-Retina and 0.94 post-surgery. The item-to-total correlation ranged from 0.50 to 0.88. Visual impairment score improved by 9 points from pre-surgery (p = 0.0003). Physical impairment score also improved from pre-surgery (p = 0.0002). ^ In conclusion, the results of this study demonstrate that the instrument is reliable and valid in patients presenting with recurrent retinal detachments. The HVAT-Retina is a simple instrument and does not burden the patient or the health professional in terms of time or cost. It may be self-administrated, not requiring an interviewer. Because the HVAT-Retina was designed to demonstrate outcomes perceivable by the patient, it has the potential to guide the decision making process between patient and physician. ^